During the past year we continued to determine the effect of treatment of a primary tumor on tumor cell kinetics and have begun to determine changes in the host immune response following removal of a primary tumor or its manipulation prior to removal. Following removal of a tumor kinetic changes were observed in a residual tumor focus within 24 hours. There was an increase in labeling index (LI) and growth fraction (GF) with minimal change in DNA synthesis (T) and cell cycle time (T). In evaluating the effect of treatment on tumor cell kinetics it was found that CY produced a depression in LI, GF and an increase in Ts. CP produced similar changes but of lesser magnitude and shorter duration. Combined therapy resulted in an augmented effect. The i.t. administration of CP resulted in a marked increase in macrophage colony production together with a consistent increase in CMA cytotoxicity. CP (i.p.) given prior to tumor removal reduced lung metastases to a greater extent than did tumor removal alone or tumor removal followed by CP. When given prior to and after removal the best effect was observed. CMA cytotoxicity and serum inhibition were influenced by lung metastases but not by the sequencing of treatment. In the coming year we will continue to evaluate the effectiveness of therapy instituted prior to tumor removal on lung metastases and will correlate findings with host parameters. We will also investigate the effects of therapy combined with tumor removal on kinetics of a residual tumor focus.